Subject-Specific Pressure Normalization of Local Pulse Wave Velocity: Separating Intrinsic From Acute Load-Dependent Stiffening in Hypertensive Patients

Abstract

Pulse wave velocity (PWV) is a powerful predictor of cardiovascular events. However, its intrinsic blood pressure (BP)-dependency complicates distinguishing between acute and chronic effects of increased BP on arterial stiffness. Based on the assumption that arteries exhibit a nearly exponential pressure-area (P-A) relationship, this study proposes a method to assess intersubject differences in local PWV independently from BP. The method was then used to analyze differences in local carotid PWV (cPWV) between hypertensive and healthy normotensive people before and after BP-normalization. Pressure (P) and diameter (D) waveforms were simultaneously acquired via tonometer at the left and ultrasound scanning at right common carotid artery (CCA), respectively, in 22 patients with Grade 1 or 2 hypertension and 22 age- and sex-matched controls. cPWV was determined using the D2P-loop method. Then, the exponential modeling of the P-area (A = πD2/4) relationships allowed defining a mathematical formulation to compute subject-specific changes in cPWV associated with BP changes, thus enabling the normalization of cPWV against intersubject differences in BP at the time of measurement. Carotid systolic BP (SBP) and diastolic BP (DBP) were, on average, 17.7 (p < 0.001) and 8.9 mmHg (p < 0.01) higher in hypertensives than controls, respectively. cPWV was 5.56 ± 0.86 m/s in controls and 6.24 ± 1.22 m/s in hypertensives. BP alone accounted for 68% of the cPWV difference between the two groups: 5.80 ± 0.84 vs. 6.03 ± 1.07 m/s after BP-normalization (p = 0.47). The mechanistic normalization of cPWV was in agreement with that estimated by analysis of covariance (ANCOVA). In conclusion, the proposed method, which could be easily implemented in the clinical setting, allows to assess the intersubject differences in PWV independently of BP. Our results suggested that mild hypertension in middle-aged subjects without target organ damage does not significantly alter the stiffness of the CCA wall independently of acute differences in BP. The results warrant further clinical investigations to establish the potential clinical utility of the method.

Estimated pulse wave velocity as a measure of vascular aging

“…This can be further complicated by the non-linear stress-strain relationship of the vessel wall such that the vessel will become stiffer with increasing distension. Empirical observations of the approximately exponential pressure-diameter relationship of arteries [ 43 ], suggests a non-linear (i.e., quadratic with negative concavity) relationship between PWV and blood pressure [ 44 ]. The equations to estimate PWV from age and mean BP include non-linear (quadratic) terms and are expected to capture both active and passive arterial stiffening to some extent.…”

Development and Clinical Validation of a Miniaturized Finger Probe for Bedside Hemodynamic Monitoring

“…In interpreting the results between PWV and ASI, it is important to understand that PWV is dependent on two intrinsic variables: arterial stiffness and BP. Due to this, PWV and ASI do not have a linear relationship [10]. As can be concluded from the results shown in Subsection 3.1, ASI does indeed hold BP information and can be used as an additional parameter for computing BP.…”

Effect of intracranial pressure on photoplethysmographic waveform in different cerebral perfusion territories: A computational study

“…The biomechanical relationship between the capacitance of common carotid artery and local blood pressure is described by a non-linear exponential function: where , , and denotes transient value of blood pressure in common carotid artery which is a major source of the capacitance effect on intracranial blood flow ( Kopustinskas et al, 2010 ). where is an established value for mean pressure of healthy adults and has been used in computational simulation studies ( Giudici et al, 2022 ). The age-dependent function is based on a large-scale physiological measurement of common carotid artery stiffness in 900 healthy subjects ( Vriz et al, 2017 ).…”

“…1 of (Kopustinskas et al, 2010), References pressure (mean pressure of healthy adults) from the subsection "Theoretical Background" and Eq. 1 of (Giudici et al, 2022), age-dependent capacitance changes from Figure 2 of (Vriz et al, 2017) ICP model Parameters of circuit elements in the ICP model: Table 1 of (Lee et al, 2015); Piecewise ICP function: References ICP value (5 mmHg) from (Ryding, 2017) and (Alperin et al, 2000); parameter in the inverse proportional function from the subsection "Assignment of Parameter Basal Values" of (Ursino and Lodi, 1997) and Figure 8 of (Ursino and Di Giammarco, 1991) PPG model Values of distal resistance and capacitance: same as those in cardiocerebral artery network; Ratios between different components: Table 1 of (Tanaka, 2022) CCA, common carotid artery; ICP, intracranial pressure; PPG, photoplethysmography.…”

“…where P ref 100 mmHg is an established value for mean pressure of healthy adults and has been used in computational simulation studies (Giudici et al, 2022). The age-dependent function is based on a large-scale physiological measurement of common carotid artery stiffness in 900 healthy subjects (Vriz et al, 2017).…”